Clinical Study

Antibiotic Stewardship Programs: Reducing Resistance and Enhancing Outcomes

Resisting Antibiotics: How Rapid PCR Testing Helps Prevent Overprescription

Steven Goldberg, MD, MBA • Apr. 2, 2025

Introduction

Antibiotic resistance is a global health crisis with severe morbidity and mortality implications. Each year, 2.8 million antibiotic-resistant infections resulting in over 35,000 deaths occur in the United States.1 When infections caused by Clostridioides difficile (C. diff) are included, this burden exceeds 3 million illnesses and 48,000 deaths.1 There have been numerous attempts at combating antibiotic resistance, chief among them are Antibiotic Stewardship Programs (ASPs) to combat inappropriate antibiotic prescribing. These increasingly popular initiatives are essential to optimize antibiotic use, reduce resistance, and improve patient outcomes. In this post, we will answer the following questions about ASPs and their ability to fight antibiotic resistance from inappropriate prescribing:

  1. What is inappropriate prescribing and how does it lead to antibiotic resistance?
  2. What are the key components of ASPs and how do they drive success?
  3. How have ASPs decreased rates of inappropriate prescribing practices nationally, and what are the clinical and cost outcomes?

The Problem: Inappropriate Prescribing Drives Antibiotic Resistance

Perhaps the greatest driver of antibiotic resistance is the pervasive problem of inappropriate prescribing. This is defined by several key criteria, including: bug-drug mismatches, unnecessarily broad-spectrum antibiotic use, excessive treatment duration, empiric antibiotic use in the setting of unconfirmed infection, and discordance with clinical guidelines.2–5 Organizations such as the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recommend many strategies employed by ASPs to combat this problem.6

In practice, common infections—including upper respiratory tract infections, acute bronchitis, sinusitis, otitis media/externa, urinary tract infections, and skin/soft tissue infections—often receive inappropriate antibiotic therapy. Many of these conditions are viral in origin or self-limiting, yet antibiotics are prescribed, resulting in unnecessary antibiotic prescriptions. In some cases, antibiotic choice is inappropriate based on the resistance mechanisms presence in the pathogen leading to exposure to ineffective antibiotics.  In patient populations at risk of severe consequences of delayed treatment, broad-spectrum antibiotics are often empirically employed to cover a range of potential pathogens pending diagnostic confirmation of infection. This can lead to overuse of extended spectrum antibiotics and, in some cases, unwarranted and prolonged treatment courses.4,6-8  Such antibiotic misuse not only contributes to antimicrobial resistance but also places patients at risk for adverse drug events.9–11

ASPs: Key Components of Successful Programs

ASPs employ a multifaceted approach to achieve success. This involves integrating various methods such as:

  1. Prospective Audit and Feedback (PAF): reviewing antibiotic prescriptions and providing feedback to prescribers in real time.6
  2. Preauthorization: requiring approval before certain antibiotics can be prescribed.6
  3. Guideline Development and Implementation: creating and disseminating clinical guidelines tailored to local resistance patterns.6
  4. Education and Training: continuous education of healthcare providers through formal training sessions, academic detailing, and informal rounds.12–14
  5. Computer-Assisted Decision Support: utilizing electronic health records and decision support systems to provide real-time guidance on antibiotic prescribing.15
  6. Antibiotic Time-Outs: periodic reassessment of ongoing antibiotic therapy to ensure its continued appropriateness.16

Success in Practice

There is an abundance of literature that supports the effectiveness of ASPs on reducing inappropriate antibiotic prescribing for many infectious diseases. Primary metrics for success include reductions in 1) the quantity of incorrect or total prescriptions and 2) decreases in overall antibiotic consumption. Important components of the metrics include de-escalation (moving from broad- to narrow-spectrum agents), and in some cases appropriate escalation, of antibiotics as well as stopping antibiotics when they are no longer indicated. ASPs span numerous healthcare settings, including intensive care units, Veterans Affairs inpatient and primary care clinics, and acute care settings in academic and non-academic hospitals.

The largest and most comprehensive analysis, published by Zay Ya et al in 2023, found that ASPs were associated with a 10% reduction in antibiotic prescriptions and a 28% reduction in antibiotic consumption.18 There is a range of outcomes in the broader literature, from an 8.2% to 74% reduction in inappropriate prescribing––however, the relative average reduction is likely between 10-34%.4,16,18–39 Cost outcomes further substantiate ASP value. Reduced antibiotic use secondary to ASP interventions has translated into lower per-patient costs, decreased pharmacy expenditure, and shortened hospital stays without sacrificing quality-adjusted life years. This has produced reductions in overall antibiotic expenditure of 17-34%.40–44

Diagnostic Testing Extends ASPs

Diagnostic testing can be considered an extension to ASP programs, or part of a “continuum” as real-time results can inform treatment decisions, strengthen antibiotic stewardship, and reduce unnecessary or inappropriate prescribing.45,46 Early identification of pathogens promotes directed treatment (i.e. alleviates the need for antibiotics altogether in some cases, reduces need for broad spectrum antibiotics in others and escalates therapy for yet others). Additionally, the ability to test for specific pathogens helps “filter out the noise” of indolent organisms that conflate the microbial picture but that aren’t relevant to the infection. Finally, quantitative reporting of microbial load for certain infectious syndromes, for example urinary and lower respiratory tract infections, provides additional information critical to informing accurate diagnoses and treatment decisions.47–50

Future Directions

National guidelines for the management of many common infectious diseases omit diagnostic testing as a component of the pathway. For example, clinical practice guidelines for management of lower respiratory infections like community acquired pneumonia (CAP) often recommend against testing (via gram stain, sputum culture, and blood culture), citing variable diagnostic accuracy of these tests and long turnaround times that delay treatment.51 However, these guidelines support use of more rapid and accurate diagnostic tests to improve treatment outcomes, especially in settings of intermediate pretest probability and/or disease severity.51,52 Molecular Testing, and specifically, Multiplex PCR testing, a type of NAAT (Nucleic Acid Amplification Test) is a rapid, sensitive, and specific diagnostic modality for the detection of various infectious organisms (in CAP and other infectious diseases), and has been shown to reduce inappropriate prescribing, lower healthcare utilization, and decrease cost of care.28,46,53–59 When next-generation diagnostics are employed in conjunction with robust ASPs, patients, providers and the public health may benefit.46,52

Antibiotic resistance remains a critical threat across all healthcare settings, driven by inappropriate prescribing and diagnostic uncertainty. ASPs serve as a cornerstone in the fight against this growing crisis––employing a comprehensive, evidence-based approach that has demonstrated significant success in optimizing antibiotic use. The integration of next-generation diagnostic testing offers the opportunity to enhance the precision of treatment decisions, reduce unnecessary antibiotic exposure, and improve both clinical and economic outcomes. As ASPs continue to evolve, leveraging these advanced technologies will be essential in preserving antibiotic efficacy, protecting patient health, and ensuring sustainable, high-quality care for future generations.

Acknowledgements

Zachary Goldberg, MD – for contributions to research and writing.

Janie French, PhD – for contributions to manuscript review and editing.

Barbara Alexander, MD – for contributions to manuscript review and editing.

References

  1. CDC. 2019 Antibiotic Resistance Threats Report. Cent Dis Control Prev. Published online July 17, 2024. Accessed January 20, 2025. https://www.cdc.gov/antimicrobial-resistance/data-research/threats/index.html
  2. Tribble AC, Lee BR, Flett KB, et al. Appropriateness of Antibiotic Prescribing in United States Children’s Hospitals: A National Point Prevalence Survey. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(8):e226-e234. doi:10.1093/cid/ciaa036
  3. Trivedi KK, Bartash R, Letourneau AR, et al. Opportunities to Improve Antibiotic Appropriateness in U.S. ICUs: A Multicenter Evaluation. Crit Care Med. 2020;48(7):968-976. doi:10.1097/CCM.0000000000004344
  4. Shively NR, Buehrle DJ, Clancy CJ, Decker BK. Prevalence of Inappropriate Antibiotic Prescribing in Primary Care Clinics within a Veterans Affairs Health Care System. Antimicrob Agents Chemother. 2018;62(8):e00337-18. doi:10.1128/AAC.00337-18
  5. Chua KP, Fischer MA, Linder JA. Appropriateness of outpatient antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study. BMJ. 2019;364:k5092. doi:10.1136/bmj.k5092
  6. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016;62(10):e51-77. doi:10.1093/cid/ciw118
  7. Nowakowska M, van Staa T, Mölter A, et al. Antibiotic choice in UK general practice: rates and drivers of potentially inappropriate antibiotic prescribing. J Antimicrob Chemother. 2019;74(11):3371-3378. doi:10.1093/jac/dkz345
  8. Smieszek T, Pouwels KB, Dolk FCK, et al. Potential for reducing inappropriate antibiotic prescribing in English primary care. J Antimicrob Chemother. 2018;73(suppl_2):ii36-ii43. doi:10.1093/jac/dkx500
  9. White AT, Clark CM, Sellick JA, Mergenhagen KA. Antibiotic stewardship targets in the outpatient setting. Am J Infect Control. 2019;47(8):858-863. doi:10.1016/j.ajic.2019.01.027
  10. Fu M, Gong Z, Zhu Y, et al. Inappropriate antibiotic prescribing in primary healthcare facilities in China: a nationwide survey, 2017-2019. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2023;29(5):602-609. doi:10.1016/j.cmi.2022.11.015
  11. Dekker ARJ, Verheij TJM, van der Velden AW. Inappropriate antibiotic prescription for respiratory tract indications: most prominent in adult patients. Fam Pract. 2015;32(4):401-407. doi:10.1093/fampra/cmv019
  12. Doernberg SB, Abbo LM, Burdette SD, et al. Essential Resources and Strategies for Antibiotic Stewardship Programs in the Acute Care Setting. Clin Infect Dis Off Publ Infect Dis Soc Am. 2018;67(8):1168-1174. doi:10.1093/cid/ciy255
  13. MacDougall C, Polk RE. Antimicrobial stewardship programs in health care systems. Clin Microbiol Rev. 2005;18(4):638-656. doi:10.1128/CMR.18.4.638-656.2005
  14. Neo JRJ, Niederdeppe J, Vielemeyer O, Lau B, Demetres M, Sadatsafavi H. Evidence-Based Strategies in Using Persuasive Interventions to Optimize Antimicrobial Use in Healthcare: a Narrative Review. J Med Syst. 2020;44(3):64. doi:10.1007/s10916-020-1531-y
  15. Fishman N. Antimicrobial stewardship. Am J Med. 2006;119(6 Suppl 1):S53-61; discussion S62-70. doi:10.1016/j.amjmed.2006.04.003
  16. Cosgrove SE, Ahn R, Dullabh P, Gordon J, Miller MA, Tamma PD. Lessons Learned from a National Hospital Antibiotic Stewardship Implementation Project. Jt Comm J Qual Patient Saf. 2024;50(6):435-441. doi:10.1016/j.jcjq.2024.04.002
  17. Moehring RW, Ashley ESD, Davis AE, et al. Development of an Electronic Definition for De-escalation of Antibiotics in Hospitalized Patients. Clin Infect Dis Off Publ Infect Dis Soc Am. 2021;73(11):e4507-e4514. doi:10.1093/cid/ciaa932
  18. Zay Ya K, Win PTN, Bielicki J, Lambiris M, Fink G. Association Between Antimicrobial Stewardship Programs and Antibiotic Use Globally: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2023;6(2):e2253806. doi:10.1001/jamanetworkopen.2022.53806
  19. Buehrle DJ, Shively NR, Wagener MM, Clancy CJ, Decker BK. Sustained Reductions in Overall and Unnecessary Antibiotic Prescribing at Primary Care Clinics in a Veterans Affairs Healthcare System Following a Multifaceted Stewardship Intervention. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(8):e316-e322. doi:10.1093/cid/ciz1180
  20. Morris AM, Bai A, Burry L, et al. Long-Term Effects of Phased Implementation of Antimicrobial Stewardship in Academic ICUs: 2007-2015. Crit Care Med. 2019;47(2):159-166. doi:10.1097/CCM.0000000000003514
  21. Campbell TJ, Decloe M, Gill S, Ho G, McCready J, Powis J. Every antibiotic, every day: Maximizing the impact of prospective audit and feedback on total antibiotic use. PLoS One. 2017;12(5):e0178434. doi:10.1371/journal.pone.0178434
  22. Peragine C, Walker SAN, Simor A, Walker SE, Kiss A, Leis JA. Impact of a Comprehensive Antimicrobial Stewardship Program on Institutional Burden of Antimicrobial Resistance: A 14-Year Controlled Interrupted Time-series Study. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(11):2897-2904. doi:10.1093/cid/ciz1183
  23. Karanika S, Paudel S, Grigoras C, Kalbasi A, Mylonakis E. Systematic Review and Meta-analysis of Clinical and Economic Outcomes from the Implementation of Hospital-Based Antimicrobial Stewardship Programs. Antimicrob Agents Chemother. 2016;60(8):4840-4852. doi:10.1128/AAC.00825-16
  24. Gohil SK, Septimus E, Kleinman K, et al. Stewardship Prompts to Improve Antibiotic Selection for Pneumonia: The INSPIRE Randomized Clinical Trial. JAMA. 2024;331(23):2007-2017. doi:10.1001/jama.2024.6248
  25. Rossin S, Barbieri E, Cantarutti A, et al. Multistep antimicrobial stewardship intervention on antibiotic prescriptions and treatment duration in children with pneumonia. PLoS One. 2021;16(10):e0257993. doi:10.1371/journal.pone.0257993
  26. Cantais A, Pillet S, Rigaill J, et al. Impact of respiratory pathogens detection by a rapid multiplex polymerase chain reaction assay on the management of community-acquired pneumonia for children at the paediatric emergency department. A randomized controlled trial, the Optimization of Pneumonia Acute Care (OPTIPAC) study. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2025;31(1):64-70. doi:10.1016/j.cmi.2024.08.001
  27. Cartuliares MB, Rosenvinge FS, Mogensen CB, et al. Evaluation of point-of-care multiplex polymerase chain reaction in guiding antibiotic treatment of patients acutely admitted with suspected community-acquired pneumonia in Denmark: A multicentre randomised controlled trial. PLoS Med. 2023;20(11):e1004314. doi:10.1371/journal.pmed.1004314
  28. Evans SE, Jennerich AL, Azar MM, et al. Nucleic Acid-based Testing for Noninfluenza Viral Pathogens in Adults with Suspected Community-acquired Pneumonia. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2021;203(9):1070-1087. doi:10.1164/rccm.202102-0498ST
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References

  1. CDC. 2019 Antibiotic Resistance Threats Report. Cent Dis Control Prev. Published online July 17, 2024. Accessed January 20, 2025. https://www.cdc.gov/antimicrobial-resistance/data-research/threats/index.html
  2. Tribble AC, Lee BR, Flett KB, et al. Appropriateness of Antibiotic Prescribing in United States Children’s Hospitals: A National Point Prevalence Survey. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(8):e226-e234. doi:10.1093/cid/ciaa036
  3. Trivedi KK, Bartash R, Letourneau AR, et al. Opportunities to Improve Antibiotic Appropriateness in U.S. ICUs: A Multicenter Evaluation. Crit Care Med. 2020;48(7):968-976. doi:10.1097/CCM.0000000000004344
  4. Shively NR, Buehrle DJ, Clancy CJ, Decker BK. Prevalence of Inappropriate Antibiotic Prescribing in Primary Care Clinics within a Veterans Affairs Health Care System. Antimicrob Agents Chemother. 2018;62(8):e00337-18. doi:10.1128/AAC.00337-18
  5. Chua KP, Fischer MA, Linder JA. Appropriateness of outpatient antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study. BMJ. 2019;364:k5092. doi:10.1136/bmj.k5092
  6. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016;62(10):e51-77. doi:10.1093/cid/ciw118
  7. Nowakowska M, van Staa T, Mölter A, et al. Antibiotic choice in UK general practice: rates and drivers of potentially inappropriate antibiotic prescribing. J Antimicrob Chemother. 2019;74(11):3371-3378. doi:10.1093/jac/dkz345
  8. Smieszek T, Pouwels KB, Dolk FCK, et al. Potential for reducing inappropriate antibiotic prescribing in English primary care. J Antimicrob Chemother. 2018;73(suppl_2):ii36-ii43. doi:10.1093/jac/dkx500
  9. White AT, Clark CM, Sellick JA, Mergenhagen KA. Antibiotic stewardship targets in the outpatient setting. Am J Infect Control. 2019;47(8):858-863. doi:10.1016/j.ajic.2019.01.027
  10. Fu M, Gong Z, Zhu Y, et al. Inappropriate antibiotic prescribing in primary healthcare facilities in China: a nationwide survey, 2017-2019. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2023;29(5):602-609. doi:10.1016/j.cmi.2022.11.015
  11. Dekker ARJ, Verheij TJM, van der Velden AW. Inappropriate antibiotic prescription for respiratory tract indications: most prominent in adult patients. Fam Pract. 2015;32(4):401-407. doi:10.1093/fampra/cmv019
  12. Doernberg SB, Abbo LM, Burdette SD, et al. Essential Resources and Strategies for Antibiotic Stewardship Programs in the Acute Care Setting. Clin Infect Dis Off Publ Infect Dis Soc Am. 2018;67(8):1168-1174. doi:10.1093/cid/ciy255
  13. MacDougall C, Polk RE. Antimicrobial stewardship programs in health care systems. Clin Microbiol Rev. 2005;18(4):638-656. doi:10.1128/CMR.18.4.638-656.2005
  14. Neo JRJ, Niederdeppe J, Vielemeyer O, Lau B, Demetres M, Sadatsafavi H. Evidence-Based Strategies in Using Persuasive Interventions to Optimize Antimicrobial Use in Healthcare: a Narrative Review. J Med Syst. 2020;44(3):64. doi:10.1007/s10916-020-1531-y
  15. Fishman N. Antimicrobial stewardship. Am J Med. 2006;119(6 Suppl 1):S53-61; discussion S62-70. doi:10.1016/j.amjmed.2006.04.003
  16. Cosgrove SE, Ahn R, Dullabh P, Gordon J, Miller MA, Tamma PD. Lessons Learned from a National Hospital Antibiotic Stewardship Implementation Project. Jt Comm J Qual Patient Saf. 2024;50(6):435-441. doi:10.1016/j.jcjq.2024.04.002
  17. Moehring RW, Ashley ESD, Davis AE, et al. Development of an Electronic Definition for De-escalation of Antibiotics in Hospitalized Patients. Clin Infect Dis Off Publ Infect Dis Soc Am. 2021;73(11):e4507-e4514. doi:10.1093/cid/ciaa932
  18. Zay Ya K, Win PTN, Bielicki J, Lambiris M, Fink G. Association Between Antimicrobial Stewardship Programs and Antibiotic Use Globally: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2023;6(2):e2253806. doi:10.1001/jamanetworkopen.2022.53806
  19. Buehrle DJ, Shively NR, Wagener MM, Clancy CJ, Decker BK. Sustained Reductions in Overall and Unnecessary Antibiotic Prescribing at Primary Care Clinics in a Veterans Affairs Healthcare System Following a Multifaceted Stewardship Intervention. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(8):e316-e322. doi:10.1093/cid/ciz1180
  20. Morris AM, Bai A, Burry L, et al. Long-Term Effects of Phased Implementation of Antimicrobial Stewardship in Academic ICUs: 2007-2015. Crit Care Med. 2019;47(2):159-166. doi:10.1097/CCM.0000000000003514
  21. Campbell TJ, Decloe M, Gill S, Ho G, McCready J, Powis J. Every antibiotic, every day: Maximizing the impact of prospective audit and feedback on total antibiotic use. PLoS One. 2017;12(5):e0178434. doi:10.1371/journal.pone.0178434
  22. Peragine C, Walker SAN, Simor A, Walker SE, Kiss A, Leis JA. Impact of a Comprehensive Antimicrobial Stewardship Program on Institutional Burden of Antimicrobial Resistance: A 14-Year Controlled Interrupted Time-series Study. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(11):2897-2904. doi:10.1093/cid/ciz1183
  23. Karanika S, Paudel S, Grigoras C, Kalbasi A, Mylonakis E. Systematic Review and Meta-analysis of Clinical and Economic Outcomes from the Implementation of Hospital-Based Antimicrobial Stewardship Programs. Antimicrob Agents Chemother. 2016;60(8):4840-4852. doi:10.1128/AAC.00825-16
  24. Gohil SK, Septimus E, Kleinman K, et al. Stewardship Prompts to Improve Antibiotic Selection for Pneumonia: The INSPIRE Randomized Clinical Trial. JAMA. 2024;331(23):2007-2017. doi:10.1001/jama.2024.6248
  25. Rossin S, Barbieri E, Cantarutti A, et al. Multistep antimicrobial stewardship intervention on antibiotic prescriptions and treatment duration in children with pneumonia. PLoS One. 2021;16(10):e0257993. doi:10.1371/journal.pone.0257993
  26. Cantais A, Pillet S, Rigaill J, et al. Impact of respiratory pathogens detection by a rapid multiplex polymerase chain reaction assay on the management of community-acquired pneumonia for children at the paediatric emergency department. A randomized controlled trial, the Optimization of Pneumonia Acute Care (OPTIPAC) study. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2025;31(1):64-70. doi:10.1016/j.cmi.2024.08.001
  27. Cartuliares MB, Rosenvinge FS, Mogensen CB, et al. Evaluation of point-of-care multiplex polymerase chain reaction in guiding antibiotic treatment of patients acutely admitted with suspected community-acquired pneumonia in Denmark: A multicentre randomised controlled trial. PLoS Med. 2023;20(11):e1004314. doi:10.1371/journal.pmed.1004314
  28. Evans SE, Jennerich AL, Azar MM, et al. Nucleic Acid-based Testing for Noninfluenza Viral Pathogens in Adults with Suspected Community-acquired Pneumonia. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2021;203(9):1070-1087. doi:10.1164/rccm.202102-0498ST
  29. Rattinger GB, Mullins CD, Zuckerman IH, et al. A sustainable strategy to prevent misuse of antibiotics for acute respiratory infections. PLoS One. 2012;7(12):e51147. doi:10.1371/journal.pone.0051147
  30. Gerber JS, Prasad PA, Fiks AG, et al. Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial. JAMA. 2013;309(22):2345-2352. doi:10.1001/jama.2013.6287
  31. Bosso JA, Drew RH. Application of antimicrobial stewardship to optimise management of community acquired pneumonia. Int J Clin Pract. 2011;65(7):775-783. doi:10.1111/j.1742-1241.2011.02704.x
  32. Leo F, Bannehr M, Valenta S, et al. Impact of a computerized physician order entry (CPOE)-based antibiotic stewardship intervention on the treatment duration for pneumonia and COPD exacerbations. Respir Med. 2021;186:106546. doi:10.1016/j.rmed.2021.106546
  33. Keller SC, Caballero TM, Tamma PD, et al. Assessment of Changes in Visits and Antibiotic Prescribing During the Agency for Healthcare Research and Quality Safety Program for Improving Antibiotic Use and the COVID-19 Pandemic. JAMA Netw Open. 2022;5(7):e2220512. doi:10.1001/jamanetworkopen.2022.20512
  34. Kelly AA, Jones MM, Echevarria KL, et al. A Report of the Efforts of the Veterans Health Administration National Antimicrobial Stewardship Initiative. Infect Control Hosp Epidemiol. 2017;38(5):513-520. doi:10.1017/ice.2016.328
  35. Shively NR, Buehrle DJ, Wagener MM, Clancy CJ, Decker BK. Improved Antibiotic Prescribing within a Veterans Affairs Primary Care System through a Multifaceted Intervention Centered on Peer Comparison of Overall Antibiotic Prescribing Rates. Antimicrob Agents Chemother. 2019;64(1):e00928-19. doi:10.1128/AAC.00928-19
  36. Stenehjem E, Wallin A, Fleming-Dutra KE, et al. Antibiotic Prescribing Variability in a Large Urgent Care Network: A New Target for Outpatient Stewardship. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;70(8):1781-1787. doi:10.1093/cid/ciz910
  37. Stenehjem E, Wallin A, Willis P, et al. Implementation of an Antibiotic Stewardship Initiative in a Large Urgent Care Network. JAMA Netw Open. 2023;6(5):e2313011. doi:10.1001/jamanetworkopen.2023.13011
  38. Balinskaite V, Johnson AP, Holmes A, Aylin P. The Impact of a National Antimicrobial Stewardship Program on Antibiotic Prescribing in Primary Care: An Interrupted Time Series Analysis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2019;69(2):227-232. doi:10.1093/cid/ciy902
  39. Li H, Gong Y, Han J, et al. Interrupted Time-Series Analysis to Evaluate the Impact of a National Antimicrobial Stewardship Campaign on Antibiotic Prescribing: A Typical Practice in China’s Primary Care. Clin Infect Dis Off Publ Infect Dis Soc Am. 2021;73(11):e4463-e4471. doi:10.1093/cid/ciaa962
  40. Yoo M, Madaras-Kelly K, Nevers M, et al. A Veterans’ Healthcare Administration (VHA) antibiotic stewardship intervention to improve outpatient antibiotic use for acute respiratory infections: A cost-effectiveness analysis. Infect Control Hosp Epidemiol. 2022;43(10):1389-1395. doi:10.1017/ice.2021.393
  41. Butler AM, Brown DS, Newland JG, et al. Comparative Safety and Attributable Healthcare Expenditures Following Inappropriate Versus Appropriate Outpatient Antibiotic Prescriptions Among Adults With Upper Respiratory Infections. Clin Infect Dis Off Publ Infect Dis Soc Am. 2023;76(6):986-995. doi:10.1093/cid/ciac879
  42. March-López P, Madridejos R, Tomas R, et al. Impact of a Multifaceted Antimicrobial Stewardship Intervention in a Primary Health Care Area: A Quasi-Experimental Study. Front Pharmacol. 2020;11:398. doi:10.3389/fphar.2020.00398
  43. Goff Z, Abbotsford J, Yeoh DK, et al. The Impact of a Multifaceted Tertiary Pediatric Hospital’s Antimicrobial Stewardship Service. Pediatr Infect Dis J. 2022;41(12):959-966. doi:10.1097/INF.0000000000003704
  44. Boyles TH, Whitelaw A, Bamford C, et al. Antibiotic stewardship ward rounds and a dedicated prescription chart reduce antibiotic consumption and pharmacy costs without affecting inpatient mortality or re-admission rates. PloS One. 2013;8(12):e79747. doi:10.1371/journal.pone.0079747
  45. Alexander BD, Irish WD, Rosato AE, et al. Is Pathogen Molecular Testing Reshaping Outpatient Antibiotic Prescribing? Am J Med Qual. 2025;40(1):21. doi:10.1097/JMQ.0000000000000214
  46. Zakhour J, Haddad SF, Kerbage A, et al. Diagnostic stewardship in infectious diseases: a continuum of antimicrobial stewardship in the fight against antimicrobial resistance. Int J Antimicrob Agents. 2023;62(1):106816. doi:10.1016/j.ijantimicag.2023.106816
  47. Pavia AT. Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2011;52 Suppl 4(Suppl 4):S284-289. doi:10.1093/cid/cir043
  48. Teepe J, Broekhuizen BDL, Loens K, et al. Disease Course of Lower Respiratory Tract Infection With a Bacterial Cause. Ann Fam Med. 2016;14(6):534-539. doi:10.1370/afm.1974
  49. Li H, Miao MX, Jia CL, et al. Interactions between Candida albicans and the resident microbiota. Front Microbiol. 2022;13:930495. doi:10.3389/fmicb.2022.930495
  50. Hashimoto S, Shime N. Evaluation of semi-quantitative scoring of Gram staining or semi-quantitative culture for the diagnosis of ventilator-associated pneumonia: a retrospective comparison with quantitative culture. J Intensive Care. 2013;1(1):2. doi:10.1186/2052-0492-1-2
  51. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST
  52. Hanson KE, Azar MM, Banerjee R, et al. Molecular Testing for Acute Respiratory Tract Infections: Clinical and Diagnostic Recommendations From the IDSA’s Diagnostics Committee. Clin Infect Dis. 2020;71(10):2744-2751. doi:10.1093/cid/ciaa508
  53. Khehra N, Padda IS, Swift CJ. Polymerase Chain Reaction (PCR). In: StatPearls. StatPearls Publishing; 2025. Accessed January 20, 2025. http://www.ncbi.nlm.nih.gov/books/NBK589663/
  54. Shiao YH. A new reverse transcription-polymerase chain reaction method for accurate quantification. BMC Biotechnol. 2003;3:22. doi:10.1186/1472-6750-3-22
  55. Gharabaghi F, Hawan A, Drews SJ, Richardson SE. Evaluation of multiple commercial molecular and conventional diagnostic assays for the detection of respiratory viruses in children. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2011;17(12):1900-1906. doi:10.1111/j.1469-0691.2011.03529.x
  56. Darie AM, Khanna N, Jahn K, et al. Fast multiplex bacterial PCR of bronchoalveolar lavage for antibiotic stewardship in hospitalised patients with pneumonia at risk of Gram-negative bacterial infection (Flagship II): a multicentre, randomised controlled trial. Lancet Respir Med. 2022;10(9):877-887. doi:10.1016/S2213-2600(22)00086-8
  57. Evans A, Doshi R, Yeaw J, et al. Healthcare utilization and costs following molecular diagnostic testing among patients with vaginitis. J Comp Eff Res. 2025;14(1):e240173. doi:10.57264/cer-2024-0173
  58. Evans A, Singh V, Upadhyay P, et al. Molecular Testing for Respiratory Tract Infections May Have Favorable Impact on Real-world Healthcare Costs. Am J Infect Dis. 2025;20(3):46-49. doi:10.3844/ajidsp.2024.46.49
  59. French AJ, Fragala MS, Evans AS, Upadhyay P, Goldberg SE, Reddy J. Real World Evaluation of Next-Day Molecular Respiratory Infectious Disease Testing on Healthcare Resource Utilization and Costs. Clin Outcomes Res CEOR. 2025;17:79-93. doi:10.2147/CEOR.S497838

Dr. Steven Goldberg

Chief Medical Officer

Dr. Steven Goldberg

Chief Medical Officer

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Resisting Antibiotics: How Rapid PCR Testing Helps Prevent Overprescription

Steven Goldberg, MD, MBA • Apr. 2, 2025

Introduction

Antibiotic resistance is a global health crisis with severe morbidity and mortality implications. Each year, 2.8 million antibiotic-resistant infections resulting in over 35,000 deaths occur in the United States.1 When infections caused by Clostridioides difficile (C. diff) are included, this burden exceeds 3 million illnesses and 48,000 deaths.1 There have been numerous attempts at combating antibiotic resistance, chief among them are Antibiotic Stewardship Programs (ASPs) to combat inappropriate antibiotic prescribing. These increasingly popular initiatives are essential to optimize antibiotic use, reduce resistance, and improve patient outcomes. In this post, we will answer the following questions about ASPs and their ability to fight antibiotic resistance from inappropriate prescribing:

  1. What is inappropriate prescribing and how does it lead to antibiotic resistance?
  2. What are the key components of ASPs and how do they drive success?
  3. How have ASPs decreased rates of inappropriate prescribing practices nationally, and what are the clinical and cost outcomes?

The Problem: Inappropriate Prescribing Drives Antibiotic Resistance

Perhaps the greatest driver of antibiotic resistance is the pervasive problem of inappropriate prescribing. This is defined by several key criteria, including: bug-drug mismatches, unnecessarily broad-spectrum antibiotic use, excessive treatment duration, empiric antibiotic use in the setting of unconfirmed infection, and discordance with clinical guidelines.2–5 Organizations such as the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recommend many strategies employed by ASPs to combat this problem.6

In practice, common infections—including upper respiratory tract infections, acute bronchitis, sinusitis, otitis media/externa, urinary tract infections, and skin/soft tissue infections—often receive inappropriate antibiotic therapy. Many of these conditions are viral in origin or self-limiting, yet antibiotics are prescribed, resulting in unnecessary antibiotic prescriptions. In some cases, antibiotic choice is inappropriate based on the resistance mechanisms presence in the pathogen leading to exposure to ineffective antibiotics.  In patient populations at risk of severe consequences of delayed treatment, broad-spectrum antibiotics are often empirically employed to cover a range of potential pathogens pending diagnostic confirmation of infection. This can lead to overuse of extended spectrum antibiotics and, in some cases, unwarranted and prolonged treatment courses.4,6-8  Such antibiotic misuse not only contributes to antimicrobial resistance but also places patients at risk for adverse drug events.9–11

ASPs: Key Components of Successful Programs

ASPs employ a multifaceted approach to achieve success. This involves integrating various methods such as:

  1. Prospective Audit and Feedback (PAF): reviewing antibiotic prescriptions and providing feedback to prescribers in real time.6
  2. Preauthorization: requiring approval before certain antibiotics can be prescribed.6
  3. Guideline Development and Implementation: creating and disseminating clinical guidelines tailored to local resistance patterns.6
  4. Education and Training: continuous education of healthcare providers through formal training sessions, academic detailing, and informal rounds.12–14
  5. Computer-Assisted Decision Support: utilizing electronic health records and decision support systems to provide real-time guidance on antibiotic prescribing.15
  6. Antibiotic Time-Outs: periodic reassessment of ongoing antibiotic therapy to ensure its continued appropriateness.16

Success in Practice

There is an abundance of literature that supports the effectiveness of ASPs on reducing inappropriate antibiotic prescribing for many infectious diseases. Primary metrics for success include reductions in 1) the quantity of incorrect or total prescriptions and 2) decreases in overall antibiotic consumption. Important components of the metrics include de-escalation (moving from broad- to narrow-spectrum agents), and in some cases appropriate escalation, of antibiotics as well as stopping antibiotics when they are no longer indicated. ASPs span numerous healthcare settings, including intensive care units, Veterans Affairs inpatient and primary care clinics, and acute care settings in academic and non-academic hospitals.

The largest and most comprehensive analysis, published by Zay Ya et al in 2023, found that ASPs were associated with a 10% reduction in antibiotic prescriptions and a 28% reduction in antibiotic consumption.18 There is a range of outcomes in the broader literature, from an 8.2% to 74% reduction in inappropriate prescribing––however, the relative average reduction is likely between 10-34%.4,16,18–39 Cost outcomes further substantiate ASP value. Reduced antibiotic use secondary to ASP interventions has translated into lower per-patient costs, decreased pharmacy expenditure, and shortened hospital stays without sacrificing quality-adjusted life years. This has produced reductions in overall antibiotic expenditure of 17-34%.40–44

Diagnostic Testing Extends ASPs

Diagnostic testing can be considered an extension to ASP programs, or part of a “continuum” as real-time results can inform treatment decisions, strengthen antibiotic stewardship, and reduce unnecessary or inappropriate prescribing.45,46 Early identification of pathogens promotes directed treatment (i.e. alleviates the need for antibiotics altogether in some cases, reduces need for broad spectrum antibiotics in others and escalates therapy for yet others). Additionally, the ability to test for specific pathogens helps “filter out the noise” of indolent organisms that conflate the microbial picture but that aren’t relevant to the infection. Finally, quantitative reporting of microbial load for certain infectious syndromes, for example urinary and lower respiratory tract infections, provides additional information critical to informing accurate diagnoses and treatment decisions.47–50

Future Directions

National guidelines for the management of many common infectious diseases omit diagnostic testing as a component of the pathway. For example, clinical practice guidelines for management of lower respiratory infections like community acquired pneumonia (CAP) often recommend against testing (via gram stain, sputum culture, and blood culture), citing variable diagnostic accuracy of these tests and long turnaround times that delay treatment.51 However, these guidelines support use of more rapid and accurate diagnostic tests to improve treatment outcomes, especially in settings of intermediate pretest probability and/or disease severity.51,52 Molecular Testing, and specifically, Multiplex PCR testing, a type of NAAT (Nucleic Acid Amplification Test) is a rapid, sensitive, and specific diagnostic modality for the detection of various infectious organisms (in CAP and other infectious diseases), and has been shown to reduce inappropriate prescribing, lower healthcare utilization, and decrease cost of care.28,46,53–59 When next-generation diagnostics are employed in conjunction with robust ASPs, patients, providers and the public health may benefit.46,52

Antibiotic resistance remains a critical threat across all healthcare settings, driven by inappropriate prescribing and diagnostic uncertainty. ASPs serve as a cornerstone in the fight against this growing crisis––employing a comprehensive, evidence-based approach that has demonstrated significant success in optimizing antibiotic use. The integration of next-generation diagnostic testing offers the opportunity to enhance the precision of treatment decisions, reduce unnecessary antibiotic exposure, and improve both clinical and economic outcomes. As ASPs continue to evolve, leveraging these advanced technologies will be essential in preserving antibiotic efficacy, protecting patient health, and ensuring sustainable, high-quality care for future generations.

Acknowledgements

Zachary Goldberg, MD – for contributions to research and writing.

Janie French, PhD – for contributions to manuscript review and editing.

Barbara Alexander, MD – for contributions to manuscript review and editing.

References

  1. CDC. 2019 Antibiotic Resistance Threats Report. Cent Dis Control Prev. Published online July 17, 2024. Accessed January 20, 2025. https://www.cdc.gov/antimicrobial-resistance/data-research/threats/index.html
  2. Tribble AC, Lee BR, Flett KB, et al. Appropriateness of Antibiotic Prescribing in United States Children’s Hospitals: A National Point Prevalence Survey. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(8):e226-e234. doi:10.1093/cid/ciaa036
  3. Trivedi KK, Bartash R, Letourneau AR, et al. Opportunities to Improve Antibiotic Appropriateness in U.S. ICUs: A Multicenter Evaluation. Crit Care Med. 2020;48(7):968-976. doi:10.1097/CCM.0000000000004344
  4. Shively NR, Buehrle DJ, Clancy CJ, Decker BK. Prevalence of Inappropriate Antibiotic Prescribing in Primary Care Clinics within a Veterans Affairs Health Care System. Antimicrob Agents Chemother. 2018;62(8):e00337-18. doi:10.1128/AAC.00337-18
  5. Chua KP, Fischer MA, Linder JA. Appropriateness of outpatient antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study. BMJ. 2019;364:k5092. doi:10.1136/bmj.k5092
  6. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016;62(10):e51-77. doi:10.1093/cid/ciw118
  7. Nowakowska M, van Staa T, Mölter A, et al. Antibiotic choice in UK general practice: rates and drivers of potentially inappropriate antibiotic prescribing. J Antimicrob Chemother. 2019;74(11):3371-3378. doi:10.1093/jac/dkz345
  8. Smieszek T, Pouwels KB, Dolk FCK, et al. Potential for reducing inappropriate antibiotic prescribing in English primary care. J Antimicrob Chemother. 2018;73(suppl_2):ii36-ii43. doi:10.1093/jac/dkx500
  9. White AT, Clark CM, Sellick JA, Mergenhagen KA. Antibiotic stewardship targets in the outpatient setting. Am J Infect Control. 2019;47(8):858-863. doi:10.1016/j.ajic.2019.01.027
  10. Fu M, Gong Z, Zhu Y, et al. Inappropriate antibiotic prescribing in primary healthcare facilities in China: a nationwide survey, 2017-2019. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2023;29(5):602-609. doi:10.1016/j.cmi.2022.11.015
  11. Dekker ARJ, Verheij TJM, van der Velden AW. Inappropriate antibiotic prescription for respiratory tract indications: most prominent in adult patients. Fam Pract. 2015;32(4):401-407. doi:10.1093/fampra/cmv019
  12. Doernberg SB, Abbo LM, Burdette SD, et al. Essential Resources and Strategies for Antibiotic Stewardship Programs in the Acute Care Setting. Clin Infect Dis Off Publ Infect Dis Soc Am. 2018;67(8):1168-1174. doi:10.1093/cid/ciy255
  13. MacDougall C, Polk RE. Antimicrobial stewardship programs in health care systems. Clin Microbiol Rev. 2005;18(4):638-656. doi:10.1128/CMR.18.4.638-656.2005
  14. Neo JRJ, Niederdeppe J, Vielemeyer O, Lau B, Demetres M, Sadatsafavi H. Evidence-Based Strategies in Using Persuasive Interventions to Optimize Antimicrobial Use in Healthcare: a Narrative Review. J Med Syst. 2020;44(3):64. doi:10.1007/s10916-020-1531-y
  15. Fishman N. Antimicrobial stewardship. Am J Med. 2006;119(6 Suppl 1):S53-61; discussion S62-70. doi:10.1016/j.amjmed.2006.04.003
  16. Cosgrove SE, Ahn R, Dullabh P, Gordon J, Miller MA, Tamma PD. Lessons Learned from a National Hospital Antibiotic Stewardship Implementation Project. Jt Comm J Qual Patient Saf. 2024;50(6):435-441. doi:10.1016/j.jcjq.2024.04.002
  17. Moehring RW, Ashley ESD, Davis AE, et al. Development of an Electronic Definition for De-escalation of Antibiotics in Hospitalized Patients. Clin Infect Dis Off Publ Infect Dis Soc Am. 2021;73(11):e4507-e4514. doi:10.1093/cid/ciaa932
  18. Zay Ya K, Win PTN, Bielicki J, Lambiris M, Fink G. Association Between Antimicrobial Stewardship Programs and Antibiotic Use Globally: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2023;6(2):e2253806. doi:10.1001/jamanetworkopen.2022.53806
  19. Buehrle DJ, Shively NR, Wagener MM, Clancy CJ, Decker BK. Sustained Reductions in Overall and Unnecessary Antibiotic Prescribing at Primary Care Clinics in a Veterans Affairs Healthcare System Following a Multifaceted Stewardship Intervention. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(8):e316-e322. doi:10.1093/cid/ciz1180
  20. Morris AM, Bai A, Burry L, et al. Long-Term Effects of Phased Implementation of Antimicrobial Stewardship in Academic ICUs: 2007-2015. Crit Care Med. 2019;47(2):159-166. doi:10.1097/CCM.0000000000003514
  21. Campbell TJ, Decloe M, Gill S, Ho G, McCready J, Powis J. Every antibiotic, every day: Maximizing the impact of prospective audit and feedback on total antibiotic use. PLoS One. 2017;12(5):e0178434. doi:10.1371/journal.pone.0178434
  22. Peragine C, Walker SAN, Simor A, Walker SE, Kiss A, Leis JA. Impact of a Comprehensive Antimicrobial Stewardship Program on Institutional Burden of Antimicrobial Resistance: A 14-Year Controlled Interrupted Time-series Study. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(11):2897-2904. doi:10.1093/cid/ciz1183
  23. Karanika S, Paudel S, Grigoras C, Kalbasi A, Mylonakis E. Systematic Review and Meta-analysis of Clinical and Economic Outcomes from the Implementation of Hospital-Based Antimicrobial Stewardship Programs. Antimicrob Agents Chemother. 2016;60(8):4840-4852. doi:10.1128/AAC.00825-16
  24. Gohil SK, Septimus E, Kleinman K, et al. Stewardship Prompts to Improve Antibiotic Selection for Pneumonia: The INSPIRE Randomized Clinical Trial. JAMA. 2024;331(23):2007-2017. doi:10.1001/jama.2024.6248
  25. Rossin S, Barbieri E, Cantarutti A, et al. Multistep antimicrobial stewardship intervention on antibiotic prescriptions and treatment duration in children with pneumonia. PLoS One. 2021;16(10):e0257993. doi:10.1371/journal.pone.0257993
  26. Cantais A, Pillet S, Rigaill J, et al. Impact of respiratory pathogens detection by a rapid multiplex polymerase chain reaction assay on the management of community-acquired pneumonia for children at the paediatric emergency department. A randomized controlled trial, the Optimization of Pneumonia Acute Care (OPTIPAC) study. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2025;31(1):64-70. doi:10.1016/j.cmi.2024.08.001
  27. Cartuliares MB, Rosenvinge FS, Mogensen CB, et al. Evaluation of point-of-care multiplex polymerase chain reaction in guiding antibiotic treatment of patients acutely admitted with suspected community-acquired pneumonia in Denmark: A multicentre randomised controlled trial. PLoS Med. 2023;20(11):e1004314. doi:10.1371/journal.pmed.1004314
  28. Evans SE, Jennerich AL, Azar MM, et al. Nucleic Acid-based Testing for Noninfluenza Viral Pathogens in Adults with Suspected Community-acquired Pneumonia. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2021;203(9):1070-1087. doi:10.1164/rccm.202102-0498ST
  29. Rattinger GB, Mullins CD, Zuckerman IH, et al. A sustainable strategy to prevent misuse of antibiotics for acute respiratory infections. PLoS One. 2012;7(12):e51147. doi:10.1371/journal.pone.0051147
  30. Gerber JS, Prasad PA, Fiks AG, et al. Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial. JAMA. 2013;309(22):2345-2352. doi:10.1001/jama.2013.6287
  31. Bosso JA, Drew RH. Application of antimicrobial stewardship to optimise management of community acquired pneumonia. Int J Clin Pract. 2011;65(7):775-783. doi:10.1111/j.1742-1241.2011.02704.x
  1. Leo F, Bannehr M, Valenta S, et al. Impact of a computerized physician order entry (CPOE)-based antibiotic stewardship intervention on the treatment duration for pneumonia and COPD exacerbations. Respir Med. 2021;186:106546. doi:10.1016/j.rmed.2021.106546
  2. Keller SC, Caballero TM, Tamma PD, et al. Assessment of Changes in Visits and Antibiotic Prescribing During the Agency for Healthcare Research and Quality Safety Program for Improving Antibiotic Use and the COVID-19 Pandemic. JAMA Netw Open. 2022;5(7):e2220512. doi:10.1001/jamanetworkopen.2022.20512
  3. Kelly AA, Jones MM, Echevarria KL, et al. A Report of the Efforts of the Veterans Health Administration National Antimicrobial Stewardship Initiative. Infect Control Hosp Epidemiol. 2017;38(5):513-520. doi:10.1017/ice.2016.328
  4. Shively NR, Buehrle DJ, Wagener MM, Clancy CJ, Decker BK. Improved Antibiotic Prescribing within a Veterans Affairs Primary Care System through a Multifaceted Intervention Centered on Peer Comparison of Overall Antibiotic Prescribing Rates. Antimicrob Agents Chemother. 2019;64(1):e00928-19. doi:10.1128/AAC.00928-19
  5. Stenehjem E, Wallin A, Fleming-Dutra KE, et al. Antibiotic Prescribing Variability in a Large Urgent Care Network: A New Target for Outpatient Stewardship. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;70(8):1781-1787. doi:10.1093/cid/ciz910
  6. Stenehjem E, Wallin A, Willis P, et al. Implementation of an Antibiotic Stewardship Initiative in a Large Urgent Care Network. JAMA Netw Open. 2023;6(5):e2313011. doi:10.1001/jamanetworkopen.2023.13011
  7. Balinskaite V, Johnson AP, Holmes A, Aylin P. The Impact of a National Antimicrobial Stewardship Program on Antibiotic Prescribing in Primary Care: An Interrupted Time Series Analysis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2019;69(2):227-232. doi:10.1093/cid/ciy902
  8. Li H, Gong Y, Han J, et al. Interrupted Time-Series Analysis to Evaluate the Impact of a National Antimicrobial Stewardship Campaign on Antibiotic Prescribing: A Typical Practice in China’s Primary Care. Clin Infect Dis Off Publ Infect Dis Soc Am. 2021;73(11):e4463-e4471. doi:10.1093/cid/ciaa962
  9. Yoo M, Madaras-Kelly K, Nevers M, et al. A Veterans’ Healthcare Administration (VHA) antibiotic stewardship intervention to improve outpatient antibiotic use for acute respiratory infections: A cost-effectiveness analysis. Infect Control Hosp Epidemiol. 2022;43(10):1389-1395. doi:10.1017/ice.2021.393
  10. Butler AM, Brown DS, Newland JG, et al. Comparative Safety and Attributable Healthcare Expenditures Following Inappropriate Versus Appropriate Outpatient Antibiotic Prescriptions Among Adults With Upper Respiratory Infections. Clin Infect Dis Off Publ Infect Dis Soc Am. 2023;76(6):986-995. doi:10.1093/cid/ciac879
  11. March-López P, Madridejos R, Tomas R, et al. Impact of a Multifaceted Antimicrobial Stewardship Intervention in a Primary Health Care Area: A Quasi-Experimental Study. Front Pharmacol. 2020;11:398. doi:10.3389/fphar.2020.00398
  12. Goff Z, Abbotsford J, Yeoh DK, et al. The Impact of a Multifaceted Tertiary Pediatric Hospital’s Antimicrobial Stewardship Service. Pediatr Infect Dis J. 2022;41(12):959-966. doi:10.1097/INF.0000000000003704
  13. Boyles TH, Whitelaw A, Bamford C, et al. Antibiotic stewardship ward rounds and a dedicated prescription chart reduce antibiotic consumption and pharmacy costs without affecting inpatient mortality or re-admission rates. PloS One. 2013;8(12):e79747. doi:10.1371/journal.pone.0079747
  14. Alexander BD, Irish WD, Rosato AE, et al. Is Pathogen Molecular Testing Reshaping Outpatient Antibiotic Prescribing? Am J Med Qual. 2025;40(1):21. doi:10.1097/JMQ.0000000000000214
  15. Zakhour J, Haddad SF, Kerbage A, et al. Diagnostic stewardship in infectious diseases: a continuum of antimicrobial stewardship in the fight against antimicrobial resistance. Int J Antimicrob Agents. 2023;62(1):106816. doi:10.1016/j.ijantimicag.2023.106816
  16. Pavia AT. Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2011;52 Suppl 4(Suppl 4):S284-289. doi:10.1093/cid/cir043
  17. Teepe J, Broekhuizen BDL, Loens K, et al. Disease Course of Lower Respiratory Tract Infection With a Bacterial Cause. Ann Fam Med. 2016;14(6):534-539. doi:10.1370/afm.1974
  18. Li H, Miao MX, Jia CL, et al. Interactions between Candida albicans and the resident microbiota. Front Microbiol. 2022;13:930495. doi:10.3389/fmicb.2022.930495
  19. Hashimoto S, Shime N. Evaluation of semi-quantitative scoring of Gram staining or semi-quantitative culture for the diagnosis of ventilator-associated pneumonia: a retrospective comparison with quantitative culture. J Intensive Care. 2013;1(1):2. doi:10.1186/2052-0492-1-2
  20. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST
  21. Hanson KE, Azar MM, Banerjee R, et al. Molecular Testing for Acute Respiratory Tract Infections: Clinical and Diagnostic Recommendations From the IDSA’s Diagnostics Committee. Clin Infect Dis. 2020;71(10):2744-2751. doi:10.1093/cid/ciaa508
  22. Khehra N, Padda IS, Swift CJ. Polymerase Chain Reaction (PCR). In: StatPearls. StatPearls Publishing; 2025. Accessed January 20, 2025. http://www.ncbi.nlm.nih.gov/books/NBK589663/
  23. Shiao YH. A new reverse transcription-polymerase chain reaction method for accurate quantification. BMC Biotechnol. 2003;3:22. doi:10.1186/1472-6750-3-22
  24. Gharabaghi F, Hawan A, Drews SJ, Richardson SE. Evaluation of multiple commercial molecular and conventional diagnostic assays for the detection of respiratory viruses in children. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2011;17(12):1900-1906. doi:10.1111/j.1469-0691.2011.03529.x
  25. Darie AM, Khanna N, Jahn K, et al. Fast multiplex bacterial PCR of bronchoalveolar lavage for antibiotic stewardship in hospitalised patients with pneumonia at risk of Gram-negative bacterial infection (Flagship II): a multicentre, randomised controlled trial. Lancet Respir Med. 2022;10(9):877-887. doi:10.1016/S2213-2600(22)00086-8
  26. Evans A, Doshi R, Yeaw J, et al. Healthcare utilization and costs following molecular diagnostic testing among patients with vaginitis. J Comp Eff Res. 2025;14(1):e240173. doi:10.57264/cer-2024-0173
  27. Evans A, Singh V, Upadhyay P, et al. Molecular Testing for Respiratory Tract Infections May Have Favorable Impact on Real-world Healthcare Costs. Am J Infect Dis. 2025;20(3):46-49. doi:10.3844/ajidsp.2024.46.49
  28. French AJ, Fragala MS, Evans AS, Upadhyay P, Goldberg SE, Reddy J. Real World Evaluation of Next-Day Molecular Respiratory Infectious Disease Testing on Healthcare Resource Utilization and Costs. Clin Outcomes Res CEOR. 2025;17:79-93. doi:10.2147/CEOR.S497838

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  47. Pavia AT. Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2011;52 Suppl 4(Suppl 4):S284-289. doi:10.1093/cid/cir043
  48. Teepe J, Broekhuizen BDL, Loens K, et al. Disease Course of Lower Respiratory Tract Infection With a Bacterial Cause. Ann Fam Med. 2016;14(6):534-539. doi:10.1370/afm.1974
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  50. Hashimoto S, Shime N. Evaluation of semi-quantitative scoring of Gram staining or semi-quantitative culture for the diagnosis of ventilator-associated pneumonia: a retrospective comparison with quantitative culture. J Intensive Care. 2013;1(1):2. doi:10.1186/2052-0492-1-2
  51. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST
  52. Hanson KE, Azar MM, Banerjee R, et al. Molecular Testing for Acute Respiratory Tract Infections: Clinical and Diagnostic Recommendations From the IDSA’s Diagnostics Committee. Clin Infect Dis. 2020;71(10):2744-2751. doi:10.1093/cid/ciaa508
  53. Khehra N, Padda IS, Swift CJ. Polymerase Chain Reaction (PCR). In: StatPearls. StatPearls Publishing; 2025. Accessed January 20, 2025. http://www.ncbi.nlm.nih.gov/books/NBK589663/
  54. Shiao YH. A new reverse transcription-polymerase chain reaction method for accurate quantification. BMC Biotechnol. 2003;3:22. doi:10.1186/1472-6750-3-22
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  56. Darie AM, Khanna N, Jahn K, et al. Fast multiplex bacterial PCR of bronchoalveolar lavage for antibiotic stewardship in hospitalised patients with pneumonia at risk of Gram-negative bacterial infection (Flagship II): a multicentre, randomised controlled trial. Lancet Respir Med. 2022;10(9):877-887. doi:10.1016/S2213-2600(22)00086-8
  57. Evans A, Doshi R, Yeaw J, et al. Healthcare utilization and costs following molecular diagnostic testing among patients with vaginitis. J Comp Eff Res. 2025;14(1):e240173. doi:10.57264/cer-2024-0173
  58. Evans A, Singh V, Upadhyay P, et al. Molecular Testing for Respiratory Tract Infections May Have Favorable Impact on Real-world Healthcare Costs. Am J Infect Dis. 2025;20(3):46-49. doi:10.3844/ajidsp.2024.46.49
  59. French AJ, Fragala MS, Evans AS, Upadhyay P, Goldberg SE, Reddy J. Real World Evaluation of Next-Day Molecular Respiratory Infectious Disease Testing on Healthcare Resource Utilization and Costs. Clin Outcomes Res CEOR. 2025;17:79-93. doi:10.2147/CEOR.S497838

Dr. Steven Goldberg

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Dr. Steven Goldberg

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